The present invention relates to hermetically sealed bags contained products used in the pharmaceutical and biotechnology processing industries and, more particularly, to the mixing of the such products while in situ within the sealed bags.
Bags containing typically fluids under highly sterile conditions are used in the bioprocessing industry for the formulation, storage, transfer and transport of fluid while maintaining the sterile conditions. Some of the characteristics of the bags to preserve the quality of the products contained within include biocompatability with the products, sterility, and non-pyrogenicity. In the biopharmaceutical processing industry, various bioprocessing steps need to be performed within bags to assure proper sterilization for the elimination of the risk of cross-contamination. The use of such bags permitting these processing steps eliminates certain otherwise necessary manual operations and thus reduce the risk of cross-contamination. In addition, the bag sealed after the addition of product eliminates the risk of airborne contamination and potentially harmful oxygen exposure. Thus the bags, typically disposed after use are a recognized efficient means to prepare and store sterile fluids. Generally, these disposable bioprocessing bags are flexible and made from compatible plastic that is sterilized by Gamma radiation. The bags can be used for all bioprocessing applications including, but not limited to, formulating, filing, storing and transporting final product, stocking pharmaceuticals in cold storage or deep freeze and finally for sampling and analytical purposes. Additionally, the bags may be used for biological fluids such as serum, buffers, and ultrapure water and also for growing cell cultures to obtain the valuable biopharmaceutical compounds produced by cells.
In many instances of the products introduced into the bags may need mixing before use. For example, the product may be formulated from the blending of dry powder into a fluid. In other situations, the product may separate during transport or storage time and require mixing before use. Finally, mixing or agitation of the product may be required for the further development of cell cultures.
There are two prior art systems that mix product within a bioprocessing bag. One utilizes non-invasive wave agitation. To accomplish this, the bioprocessing bag is placed in a pan and subject to a controlled rocking motion. This wave agitation creates wave motions within the sealed bag to produce product homogeneity. Another mixing apparatus utilizes a peristaltic pump that squeezes the disposable bioprocessing bag in order to agitate and mix the product within the bag.
The rocking action mixing apparatus typically works best with small volumes and frequently proves to be unsatisfactory for tough mixing situations such as with the dissolving of powders. Often the powders are incompletely placed into a homogeneous solution unless the apparatus is operated for unacceptable lengths of time. The squeezing action of the peristaltic pump can crush living cells through the pressure it applies to the tube to induce circulation. Because each of the bags has a seal at one end, the movement caused by the rocking and/or peristaltic action may cause failure of the seal, allowing contaminants to enter the bag.
It is therefore a paramount object of the present invention to provide a simple, yet effective apparatus and method for mixing materials into final non-contaminated product in sterilized disposable bags. The present invention addresses and corrects problems of the prior art and provides benefits beyond those contemplated by the use of either the wave mixing system or the peristaltic pump system.
This and other objects and advantages of the present invention will become apparent upon a reading of the following description and appended claims.
The present invention pertains to a biprocessing bag that contains a mixing element within that can be rotated or agitated without the introduction of contaminants into the bioprocessing bag. The mixing element within the bag includes a flexible tube extending substantially the entire length of the bag. In accordance to one embodiment of the invention, the tube is has a closed distal end within the bag and extends outwardly through a seal and has an open end adapted to accept a more rigid mixing rod of a predetermined shape. The tube is provided with annularly shaped, spaced apart ribs or inserts internally positioned that function to prevent the rigid rod from contacting the tube while it is being threaded into the tube and reduce the friction between the rod and flexible tube. The flexible tube thus takes on the shape of the rod when in position within the tube. The bag is typically placed into a rigid container and clamped about the neck of the bag where the seal is located. The rod is operatively coupled to a drive shaft of a motor and during operation causes the flexible tube to move with the rod for axial or radial mixing of the product contained within the bag. Preferably the shape of the rod is balanced so as not to introduce significant and undesirable vibrations into the bag during operation.